Proposed is a continued development of QR206, which comprises epothilone D (EpoD), a highly toxic chemotherapy in its free form, reformulated into long acting poly(lactic-co-glycolic) acid microparticles that provide 6-8 weeks of sustained release within tumors and lymph nodes, as treatment of head and neck squamous cell carcinoma (HNSCC). Intratumoral (i.t.) injection of QR206 delivers EpoD in poly-disperse microparticles spanning both large sizes that remain trapped at the tumor site and small sizes that spread into regional and lymphoid tissues by harnessing the migration of phagocytic cells, such as APCs. The proposed formulation will reduce the amount of drug required to treat the tumor and the systemic exposure to it, thus reducing side effects and systemic toxicity. The proposed IND-enabling studies will include dose escalation and biodistribution studies in immunocompetent BALB/c mice bearing established oral syngeneic tumors (Objectives 1 and 2, respectively). Successful murine studies will be followed by a dose escalation veterinary trial conducted where oral squamous cell carcinomas in cats will be treated with single doses of QR206 (Objective 3). The expected results include establishment of the efficacy and safety in two animal models and confirming QR206's targeting mechanism and anticipated biodistribution.